In recent years, the abuse of prescription and over-the-counter (OTC) pharmaceutical products has become a concerning trend. For example, in some instances, potential abusers simultaneously ingest one or more prescription or over-the-counter pharmaceuticals in combination with alcohol in order to increase the effect of the alcohol and/or the specific drug substances contained in the pharmaceutical product. In particular, certain pharmaceutical products for oral administration release the drug substance contained therein at a faster rate in the presence of alcohol and, accordingly, the drug substance is available for absorption at a faster rate than intended by the manufacturer. Such a faster release rate may lead to unwanted and potentially dangerous effects.
An unintended rapid release of all or a significant fraction of a drug substance contained within a pharmaceutical composition over a short period of time is often referred to as “dose dumping”. In the context of modified-release pharmaceutical compositions (e.g., sustained or controlled release pharmaceutical compositions), which are often formulated to include relatively high amounts of drug substance in order to preserve a therapeutic benefit over an extended period of time, some compositions have been reported to contain drug substances and excipients that exhibit higher solubility in ethanolic solutions than in aqueous solutions that are free of ethanol. Such compositions have the potential to exhibit relatively high rates of drug dissolution and increased release rates of drug substance in the presence of ethanol. Therefore, consumption of alcoholic beverages in combination with modified-release compositions that exhibit increase release rates of drug substance in the presence of ethanol has the potential to induce dose dumping, which may increase the ease with which such modified-release compositions can be abused. However, the potential problems resulting from dose dumping in the presence of ethanol are not limited to modified-release compositions. Conventional oral compositions (e.g., immediate release compositions dosage forms) may also exhibit dose dumping behaviour in the presence of ethanol, which, in turn, can result in even more rapid delivery and uptake of the drug substance or easier isolation of the drug substance from formulation excipients and/or other inactive constituents included in the pharmaceutical product.
In the 1990s, the U.S. Food and Drug Administration (FDA) required that certain OTC pain relievers and fever reducers carry a warning label advising consumers who consume three or more alcoholic drinks every day to consult a physician before using such products. FDA issued this final rule after considering public comments and data on the effects of combining chronic alcohol ingestion and the use of various OTC analgesics. The action also followed the recommendations of the Nonprescription Drugs Advisory Committee and the Arthritis Drugs Advisory Committee, which concluded that chronic alcohol users should be warned that they may be at an increased risk of liver damage or stomach bleeding from use of these drugs. Drug substances affected by this labelling requirement include, for example, aspirin, other salicylates, acetaminophen, ibuprofen, naproxen sodium, and ketoprofen.